Effect of Oral Appliance Therapy on Upper Airway
Collapsibility in Obstructive Sleep Apnea
Andrew T Ng, Helen Gotsopoulos, Jin Qian, and Peter A Cistulli
Department of Respiratory and Sleep Medicine, St. George Hospital, University of New South Wales, Sydney, Australia
Oral appliance therapy is emerging as an alternative to continuous
positive airway pressure for the treatment of obstructive sleep apnea
(OSA). However, its precise mechanisms of action are yet to be de-
fined. We examined the effect of a mandibular advancement splint
(MAS) on upper airway collapsibility during sleep in OSA. Ten patients
with proven OSA had a custom-made MAS incrementally adjusted
during an acclimatization period until the maximum comfortable
limit of mandibular advancement was reached. Polysomnography
with the splint was then performed. After a 1-week washout period,
upper airway closing pressures during sleep (with and without MAS)
were determined. Significant improvements with MAS therapy
were seen in the apnea/hypopnea index (25.0 3.1 vs. 13.2 4.5/
hour, p 0.03) and upper airway closing pressure in Stage 2 sleep
(1.6 0.4 vs. 3.9 0.6 cm H2O, p 0.01) and in slow wave sleep
(2.5 0.7 vs. 4.7 0.6 cm H2O, p 0.02) compared with no
therapy. These preliminary data indicate that MAS therapy is associ-
ated with improved upper airway collapsibility during sleep. The
mediators of this effect remain to be determined.
Keywords: mandibular advancement splint; obstructive sleep apnea;
upper airway collapsibility
Obstructive sleep apnea (OSA) is a common disorder occurring
in around 4% of men and 2% of women in the middle-aged
workforce (1). It is characterized by recurrent obstruction of
the upper airway during sleep (2). The current treatment of
choice is continuous positive airway pressure delivered via
a nasal mask to the upper airway during sleep (3). This is
an extremely effective treatment, but its cumbersome nature
often leads to reduced tolerance and compliance (46). An
emerging treatment alternative is oral appliance therapy (7),
which has potential advantages over continuous positive air-
way pressure because it is less obtrusive, does not make noise,
and is more portable. Of the five randomized crossover trials
comparing continuous positive airway pressure with oral appli-
ances (812), all but one (12) demonstrated a patient pref-
erence in favor of oral appliances. However, although oral
appliance therapy has been shown to be effective across all
grades of OSA severity (13, 14), a key limitation is reduced
effectiveness compared with continuous positive airway pres-
sure (812).
Current understanding of the precise mechanisms of ac-
tion of oral appliances in OSA is incomplete. A better un-
derstanding of these mechanisms could improve our ability
to predict treatment outcome, a key unresolved issue. Intu-
itively, one would believe that mandibular advancement
should improve the anteroposterior dimension of the oro-
pharynx. However, recent studies suggest that increases in
(Received in original form November 4, 2002; accepted in final form April 28, 2003)
Correspondence and requests for reprints should be addressed to Peter Cistulli,
M.D., Ph.D., Department of Respiratory Medicine, St. George Hospital, Belgrave
Street, Kogarah, NSW 2217, Australia. E-mail: p.cistulli@unsw.edu.au
Am J Respir Crit Care Med Vol 168. pp 238241, 2003
Originally Published in Press as DOI: 10.1164/rccm.200211-1275OC on April 30, 2003
Internet address: www.atsjournals.org
upper airway caliber occur in the lateral dimension at the
level of the velopharynx (15, 16). Hence, the anatomic changes
induced by mandibular advancement appear to be quite com-
plex, presumably due to the intricate linkages between upper
airway structures. Regardless of these anatomic changes, the
ultimate determinant of upper airway closure is the degree
of upper airway collapsibility during sleep. Abnormal upper
airway collapsibility during sleep has been clearly documented
in both snorers and patients with OSA compared with normals
(17, 18). Furthermore, treatment of OSA by weight loss or
surgery has been shown to improve upper airway collapsibility
in responders (19, 20). We postulate that oral appliance ther-
apy reduces upper airway collapsibility during sleep. Hence,
our aim was to examine the effect of oral appliance therapy
on upper airway collapsibility during sleep.
METHODS
Study Population
Adult patients were recruited from a multidisciplinary Sleep Disorders
Clinic in a University Teaching Hospital. Inclusion criteria were the
presence of at least two symptoms of OSA (snoring, fragmented sleep,
witnessed apneas, daytime sleepiness) and evidence of OSA on polys-
omnography, with an apnea/hypopnea index (AHI) of 10/hour or more.
Patients were excluded if there was evidence of periodontal disease, dental
caries, edentulism, an exaggerated gag reflex, or predominant central sleep
apnea on polysomnography. The study was approved by the institutional
Ethics Committee, and written informed consent was obtained from all
patients before commencement. We used a mandibular advancement splint
(MAS) as described previously by our group (13, 14).
Study Design
A prospective study design was used. Each patient underwent three
sleep studies. The first diagnostic polysomnogram confirmed an AHI
of more than 10/hour and was performed before study commencement.
After an acclimatization period during which incremental anterior ad-
justments of the mandible were made until the maximum comfortable
limit was reached, an additional polysomnogram was performed with
the MAS to determine treatment efficacy. Patients then underwent no
treatment during a 1-week washout period. A final sleep study was then
performed, solely for the purpose of making upper airway closing pressure
(UACP) measurements, with and without the MAS (treatment order
was randomly assigned within this study night).
Outcome Measures
Polysomnography. Standard nocturnal polysomnography was performed
as described previously (13, 14). Sleep recordings were scored in a standard
fashion (21, 22) by an experienced polysomnographer who was blinded
to the patients treatment.
UACP. The technique used to measure UACP was first reported
by Issa and Sullivan (17, 18). Patients slept in the supine position with
the head and neck kept in the neutral position. A specially designed
nose mask system was used, allowing for the provision of continuous
positive airway pressure as well as complete external occlusion at the
nose. Complete external nasal occlusion applied at end-expiration causes
each inspiratory effort to produce a progressive increase in suction
pressure to a maximum value, followed by a rapid return to baseline.
Each subsequent occluded inspiratory effort produces a larger (more
subatmospheric) increase in nasal pressure until a critical pressure is
Ng, Gotsopoulos, Qian, et al.: Oral Appliances in Sleep Apnea
reached, at which point the nasal pressure ceases to increase despite
increasing inspiratory efforts as evidenced by the increasing respitrace
and diaphragm EMG activity. This critical pressure has been defined as
the UACP. A typical recording from one of the study patients is shown
in Figure 1. The more negative the UACP, the less collapsible the air-
way. Two qualitatively different patterns of response to nasal occlusion
have been identified (17). In the most commonly seen type 1 response,
the airway closure occurs only during the inspiratory phase. In the type
2 response, the critical pressure reached during inspiration is also main-
tained during expiration, indicating complete obstruction during both
phases of the respiratory cycle. Multiple measurements were taken in
each of the conditions and were highly reproducible. The validity of this
technique has been verified by concurrent measurement of esophageal
and tracheal pressures (17).
Treatment Outcome
Complete response was defined as a resolution of symptoms and reduc-
tion in AHI to less than 5/hour. Partial response was defined as im-
proved symptoms plus a 50% reduction or more in AHI but remaining
5/hour or more. Failure was defined as less than 50% reduction in AHI.
Statistical Analysis
Data were analyzed using a statistical package (SPSS Version 8.0; SPSS
Inc, Chicago, IL). Paired t tests were used to compare clinical and physio-
logic variables before and after MAS treatment. Correlation analysis was
performed using Spearmans rank correlation coefficient for nonparamet-
ric data. The MannWhitney U test was used to compare UACP measure-
ments between treatment outcome groups. All descriptive statistics are
presented as mean SD. Estimated means are presented as mean
SEM.
RESULTS
Study Population
The study sample consisted of 10 patients (nine males and one
female), all of whom completed the protocol. Patient characteris-
tics at baseline are presented in Table 1. There was no significant
difference between baseline and treatment regarding weight.
The mean mandibular advancement with the MAS was 4.6
1.4 mm (range, 3.08.0) from centric occlusion.
Outcomes
The MAS was well tolerated. Only mild side effects were experi-
enced, which included excessive salivation, gum irritation, mouth
dryness, and jaw discomfort. These did not preclude use of the
MAS.
Polysomnographic outcomes are summarized in Table 2. MAS
treatment resulted in a significant reduction in AHI and a significant
increase in minimum SaO2. The MAS resulted in complete response
in five patients (50%), partial response in two patients (20%),
and treatment failure in three patients (30%). Six patients (60%)
achieved an AHI of less than 10/hour.
239
TABLE 1. BASELINE CHARACTERISTICS OF PATIENTS
Variable Mean SD (n 10 ) Range
Sex, male/female 9/1
Age, yr 44 12 2858
BMI, kg/m2 30.8 6.2 24.646.8
Neck circumference, cm 40.3 0.5 38.042.5
AHI, h1 25.0 9.8 14.644.6
MinSaO2, % 86 4 7993
Definition of abbreviations: AHI apnea/hypopnea index; BMI body mass
index; MinSaO2 minimum SaO2.
MAS treatment resulted in significant improvements in UACP
during Stage 2 non-REM sleep and slow wave sleep (Table 2).
Improvement was noted in all subjects, albeit to different degrees.
Nine patients had the type 1 response with and without MAS.
One patient had the type 2 response without MAS, converting
to a type 1 response with MAS.
A significant positive correlation was found between the
change in AHI and change in UACP in Stage 2 non-REM sleep
(r 0.64, p 0.05). A median improvement in UACP (Stage 2
non-REM sleep) of 2.8 cm H2O (25th, 75th percentiles 1.9, 5.7)
was observed in the complete responders, and this was significantly
greater than the median of 1.1 cm H2O (25th, 75th percentiles:
0.6, 1.2) seen in the combined group of partial responders and
treatment failures (MannWhitney U: z 2.41, p 0.01).
No significant correlation was found between baseline UACP
and AHI or between the degree of mandibular advancement and
change in UACP.
DISCUSSION
Despite the increasing use of oral appliances in the treatment of
OSA, considerable uncertainty about their precise mechanisms
of action exists. This is the first study to examine the influence of
an oral appliance on UACP during sleep. We found that the MAS
improved upper airway collapsibility and suggest that this is one
mechanism through which OSA is improved.
Upper airway patency is complex and involves a number of
interrelated factors. A balance exists between its tendency to
collapse, induced by the subatmospheric intraluminal pressure
during inspiration, and upper airway dilator muscle activity, which
is influenced by upper airway dimensions and complex neuromus-
cular reflex interactions (2). Upper airway collapsibility measured
by the UACP is likely to reflect the net effect of all these factors.
Our patients had a baseline average UACP of 1.6 0.4 cm H2O
in Stage 2 sleep and 2.5 0.7 cm H2O in slow wave sleep during
supine sleep. These results are consistent with previous findings
in patients with OSA by Issa and Sullivan (17).
Figure 1. Polygraph record showing a typical type 1 nasal
occlusion test during Stage 2 nonrapid eye movement
sleep in a patient with obstructive sleep apnea (OSA).
Complete external nasal airway occlusion was applied at
end-expiration (first arrow). Note that at a critical nasal
pressure (Pn 6.1 cm H2O) the fifth and sixth occluded
breaths have a prominent inspiratory plateau despite a
progressive increase in diaphragm EMG (EMG d) activity
and respitrace (chest and abdomen) deflection through-
out the occluded period. The inflection point in the nasal
pressure trace indicates the closing pressure of the upper
airway. Occlusion was released at the second arrow, fol-
lowed by an arousal. Inspiration is downward.
240 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 168 2003
TABLE 2. OUTCOME MEASUREMENTS
Variable No MAS MAS p Value
BMI, kg/m2 30.8 6.2* 30.9 6.1 0.4
Neck circumference, cm 40.3 0.5* 40.4 0.5 0.6
AHI, h1 25.0 3.1* 13.2 4.5 0.03
MinSaO2, % 86 6* 90 3 0.01
UACP Stage 2 NREM, cm H2O 1.6 1.4 3.9 1.9 0.01
UACP SWS, cm H2O 2.5 1.9 4.7 1.7 0.02
Definition of abbreviations: AHI apnea/hypopnea index; BMI body mass
index; MAS mandibular advancement splint; MinSaO2 minimum SaO2; UACP
Stage 2 NREM upper airway closing pressure during Stage 2 nonrapid eye
movement sleep; UACP SWS upper airway closing pressure during slow wave
sleep.
Comparison made using paired t test.
Data are presented as mean SEM.
* Data obtained from baseline polysomnogram (without MAS).
Data obtained from polysomnogram with MAS.
Data obtained from closing pressure determination sleep study.
This study demonstrated a relationship between the magni-
tude of improvement in UACP during Stage 2 sleep and the
improvement in AHI. In addition, the improvement in UACP
during Stage 2 sleep in the group of complete responders was
significantly greater than that found in the other two groups com-
bined. However, an interesting finding in our study was that UACP
improved after MAS treatment even in the failures, albeit to a
lesser extent. This suggests that it is the magnitude of improvement
in UACP that determines treatment outcome. How mandibular
advancement improves upper airway collapsibility, however, re-
mains unclear. Anatomic improvements in the anteroposterior
dimension of the oropharynx have been postulated, although re-
cent studies (15, 16) suggest that it is the lateral dimensions of
the velopharynx that improve. Another mechanism proposed by
Isono and coworkers (23) is that mandibular advancement
stretches the soft palate, thus stiffening the velopharynx because
of the connection of the lateral wall of the soft palate to the base
of the tongue through the palatoglossal arch.
Improved upper airway collapsibility has been seen when other
treatment alternatives have been successful. Schwartz and cowork-
ers (19, 20) have demonstrated improvements in upper airway
collapsibility after treatment success with weight loss and also
with uvulopalatopharyngoplasty using a technique called the pha-
ryngeal critical pressure. This technique, which is different from
the closing pressure technique used in our study, examines pres-
sureflow relationships during sleep using the Starling resistor
model (flow through a collapsible conduit) of the upper airway.
Pharyngeal critical pressure is the pressure below which occlusion
and cessation of airflow occurs. This pressure is found by measur-
ing maximal airflow at different nasal mask pressures and then
extrapolating to the pressure at which no airflow occurs (24).
Therefore, pharyngeal critical pressure is a derived value and
is believed to represent the pressure surrounding the locus of
pharyngeal collapse. This model predicts that when pharyngeal
critical pressure is positive relative to atmospheric nasal pressure,
the upper airway should close. The closing pressure technique
that we used measures the airway suction pressure at which
pharyngeal closure occurs in response to complete external nasal
occlusion, which is fundamentally different from the pharyngeal
critical pressure technique. We chose the closing pressure tech-
nique because it provides a direct measure of the pressure at
which airway collapse occurs.
In our study, the average mandibular protrusion of 4.6 mm is
less than that seen in other studies (13, 14). This was the maximum
comfortable limit tolerated by our study patients and was 65%
of the maximum possible protrusion on average.
One potential limitation of our study was treatment order
bias because UACP measurements were made with and without
MAS during a single night. This was reduced by randomizing
the treatment order during the closing pressure determination
study. As a result of the unpredictability of achieving REM sleep
during the overnight protocol, only two patients had reliable
UACP determinations in this sleep stage. Another limitation was
the inability of the technique to localize the site(s) of obstruction
within in the upper airway. This could be overcome in future
studies by using a catheter measuring pressure at different levels
in the upper airway during a closing pressure determination
study. Although the sample studied was small, there was unifor-
mity of the direction of effect in all patients.
In conclusion, we have demonstrated that oral appliance ther-
apy improves upper airway collapsibility during sleep in patients
with OSA. The magnitude of improvement in UACP was greater
in patients who achieved a complete response to treatment. Given
that treatment success with MAS is not achievable in every patient,
further research is needed to determine whether UACP can be
used as a predictor of treatment outcome.
Acknowledgment : The authors thank Carol Chen and Michael Lazaris for assisting
with patient management and technical support. The oral appliance used in this
study was designed by Dr. Richard Palmisano (patents pending).
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